The purpose of this project is to understand the molecular mechanism by which genes for connective tissue proteins are differentially regulated and expressed during normal development and in disease states. We are using recombinant DNA technology and conventional methods in nucleic acid biochemistry to study the structure and expression of genes coding for extracellular and cell-associated structural proteins that are affected during morphogenesis and in pathologic states. To study normal and abnormal cartilage development, we are examining the molecular basis for loss of the phenotypic traits of chondrocytes after exposure to the thymidine analog 5-bromodeoxyuridine. Recombinant cDNA and genomic clones of collagen types I and II are being used to analyze the RNA and DNA of differentiated and dedifferentiated cartilage cells. In addition, the expression of genes encoding basement membrane constituents (type IV collagen and laminin) is being examined by biosynthetic studies and by analysis of the RNA of the basement membrane producing EHS tumor. We have also synthesized a recombinant cDNA clone coding for the mouse. 1(I) collagen chain, to study variations in type I collagen synthesis in murine cells after exposure to tumor promotors.